CRHR2 (Corticotropin-Releasing Hormone Receptor 2) in the Nucleus of the Solitary Tract Contributes to Intermittent Hypoxia-Induced Hypertension.

Abstract

This study tested the hypothesis that CRHRs (corticotropin-releasing hormone receptors) in the nucleus of the solitary tract (NTS) contribute to the hypertension induced by intermittent hypoxia (IH) exposure in rats. Initial studies using in situ hybridization revealed low mRNA level of CRHR1 (CRH type 1 receptor) but high mRNA level of CRHR2 (CRH type 2 receptor) in the NTS. Calcium imaging studies on NTS slice preparations using Fura-2-acetoxymethyl ester demonstrated that CRH induced a transient increase of intracellular calcium level. The CRH-induced calcium response was reproduced in the presence of TTX (tetrodotoxin) but was abolished by depletion of extracellular calcium or by the L-type calcium channel blocker Nifedipine. The CRH-induced calcium influx was attenuated by the CRHR2 antagonist K41498 but not by the CRHR1 antagonist NBI-35 965. Calcium influx can be induced by the CRHR2 agonist Urocortin II but not by the CRHR1 agonist Stressin 1. IH exposure did not affect CRHR1 mRNA level but significantly decreased CRHR2 mRNA level and the CRH-induced calcium influx in the NTS. Further in vivo studies showed that intra-fourth ventricle infusion of K41498 did not affect the basal blood pressure but significantly attenuated the IH-induced hypertension; intra-fourth ventricle infusion of Urocortin II significantly increased basal blood pressure and exacerbated the IH-induced hypertension. Collectively, these results suggest that CRHR2 in the NTS contributes to the IH-induced hypertension; downregulation of CRHR2 and CRHR2-mediated calcium influx in the NTS may serve as an adaptive response to protect against the IH-induced hypertension.

• Authors: Lei A Wang, Dianna H Nguyen, Steve W Mifflin
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 72 Issue 4 Pg. 994-1001 (10 2018) ISSN: 1524-4563 [Electronic] United States
• PMID: 30354709 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Amphibian Proteins
• CRF receptor type 2
• Calcium Channel Blockers
• Peptide Hormones
• Receptors, Corticotropin-Releasing Hormone
• Urocortins
• CRF receptor type 1
• sauvagine
• Nifedipine
• Calcium

Topics

• Amphibian Proteins (pharmacology)
• Animals
• Autonomic Nervous System (metabolism)
• Calcium (metabolism)
• Calcium Channel Blockers (pharmacology)
• Hypertension (drug therapy, etiology, metabolism)
• Hypoxia (complications, metabolism)
• Nifedipine (pharmacology)
• Peptide Hormones (pharmacology)
• Rats
• Receptors, Corticotropin-Releasing Hormone (metabolism)
• Solitary Nucleus (metabolism)
• Urocortins (pharmacology)